tbuckley/cabot-search huggingface dataset:
Natriuresis-guided diuretic therapy in acute heart failure: a pragmatic randomized trial
Authors: Jozine M. ter Maaten, Iris E. Beldhuis, Peter van der Meer, Jan A. Krikken, Douwe Postmus, Jenifer E. Coster, Wybe Nieuwland, Dirk J. van Veldhuisen, Adriaan A. Voors, Kevin Damman
Journal: Nature Medicine (2023)

Measurement of natriuresis has been suggested as a reliable, easily obtainable biomarker for assessment of the response to diuretic treatment in patients with acute heart failure (AHF). Here, to assess whether natriuresis-guided diuretic therapy in patients with AHF improves natriuresis and clinical outcomes, we conducted the pragmatic, open-label Pragmatic Urinary Sodium-based algoritHm in Acute Heart Failure trial, in which 310 patients (45% female) with AHF requiring treatment with intravenous loop diuretics were randomly assigned to natriuresis-guided therapy or standard of care (SOC). In the natriuresis-guided arm, natriuresis was determined at set timepoints, prompting treatment intensification if spot urinary sodium levels were <70 mmol l-1. The dual primary endpoints were 24 h urinary sodium excretion and a combined endpoint of time to all-cause mortality or adjudicated heart failure rehospitalization at 180 days. The first primary endpoint was met, as natriuresis in the natriuresis-guided and SOC arms was 409 ± 178 mmol arm versus 345 ± 202 mmol, respectively (P = 0.0061). However, there were no significant differences between the two arms for the combined endpoint of time to all-cause mortality or first heart failure rehospitalization, which occurred in 46 (31%) and 50 (31%) of patients in the natriuresis-guided and SOC arms, respectively (hazard ratio 0.92 [95% confidence interval 0.62-1.38], P = 0.6980). These findings suggest that natriuresis-guided therapy could be a first step towards personalized treatment of AHF. ClinicalTrials.gov registration: NCT04606927 .
Reduced Progenitor Function and Altered Immune Landscape Contribute to Field Cancerization of Lung Adenocarcinoma
Authors: Alexis Assante, Khosbayar Lkhagvadorj, Eric T. Clambey, Thomas Danhorn, Daniel T. Merrick, Robert L. Keith, Melissa L. New, James Degregori, York E. Miller, Moumita Ghosh
Journal: American Journal of Respiratory and Critical Care Medicine (2023)
Propagation of activity through the cortical hierarchy and perception are determined by neural variability
Authors: James M. Rowland, Thijs L. van der Plas, Matthias Loidolt, Robert M. Lees, Joshua Keeling, Jonas Dehning, Thomas Akam, Viola Priesemann, Adam M. Packer
Journal: Nature Neuroscience (2023)

Abstract Brains are composed of anatomically and functionally distinct regions performing specialized tasks, but regions do not operate in isolation. Orchestration of complex behaviors requires communication between brain regions, but how neural dynamics are organized to facilitate reliable transmission is not well understood. Here we studied this process directly by generating neural activity that propagates between brain regions and drives behavior, assessing how neural populations in sensory cortex cooperate to transmit information. We achieved this by imaging two densely interconnected regions—the primary and secondary somatosensory cortex (S1 and S2)—in mice while performing two-photon photostimulation of S1 neurons and assigning behavioral salience to the photostimulation. We found that the probability of perception is determined not only by the strength of the photostimulation but also by the variability of S1 neural activity. Therefore, maximizing the signal-to-noise ratio of the stimulus representation in cortex relative to the noise or variability is critical to facilitate activity propagation and perception.
Intravital measurements of solid stresses in tumours reveal length-scale and microenvironmentally dependent force transmission
Authors: Sue Zhang, Gabrielle Grifno, Rachel Passaro, Kathryn Regan, Siyi Zheng, Muhamed Hadzipasic, Rohin Banerji, Logan O’Connor, Vinson Chu, Sung Yeon Kim, Jiarui Yang, Linzheng Shi, Kavon Karrobi, Darren Roblyer, Mark W. Grinstaff, Hadi T. Nia
Journal: Nature Biomedical Engineering (2023)
Odour-imagery ability is linked to food craving, intake, and adiposity change in humans
Authors: Emily Perszyk, Xue Davis, Jelena Djordjevic, Marilyn Jones-Gotman, Jessica Trinh, Zach Hutelin, Maria Veldhuizen, Leonie Koban, Tor Wager, Hedy Kober, Dana Small
Journal: Nature Metabolism (2023)
Tumor-specific cholinergic CD4+ T lymphocytes guide immunosurveillance of hepatocellular carcinoma
Authors: Chunxing Zheng, Bryan E. Snow, Andrew J. Elia, Robert Nechanitzky, Carmen Dominguez-Brauer, Shaofeng Liu, Yin Tong, Maureen A. Cox, Enrico Focaccia, Andrew C. Wakeham, Jillian Haight, Chantal Tobin, Kelsey Hodgson, Kyle T. Gill, Wei Ma, Thorsten Berger, Mathias Heikenwälder, Mary E. Saunders, Jerome Fortin, Suet Yi Leung, Tak W. Mak
Journal: Nature Cancer (2023)

Cholinergic nerves are involved in tumor progression and dissemination. In contrast to other visceral tissues, cholinergic innervation in the hepatic parenchyma is poorly detected. It remains unclear whether there is any form of cholinergic regulation of liver cancer. Here, we show that cholinergic T cells curtail the development of liver cancer by supporting antitumor immune responses. In a mouse multihit model of hepatocellular carcinoma (HCC), we observed activation of the adaptive immune response and induction of two populations of CD4+ T cells expressing choline acetyltransferase (ChAT), including regulatory T cells and dysfunctional PD-1+ T cells. Tumor antigens drove the clonal expansion of these cholinergic T cells in HCC. Genetic ablation of Chat in T cells led to an increased prevalence of preneoplastic cells and exacerbated liver cancer due to compromised antitumor immunity. Mechanistically, the cholinergic activity intrinsic in T cells constrained Ca2+-NFAT signaling induced by T cell antigen receptor engagement. Without this cholinergic modulation, hyperactivated CD25+ T regulatory cells and dysregulated PD-1+ T cells impaired HCC immunosurveillance. Our results unveil a previously unappreciated role for cholinergic T cells in liver cancer immunobiology.
A critical period plasticity framework for the sensorimotor–association axis of cortical neurodevelopment
Authors: Bart Larsen, Valerie J. Sydnor, Arielle S. Keller, B.T. Thomas Yeo, Theodore D. Satterthwaite
Journal: Trends in Neurosciences (2023)

To understand human brain development it is necessary to describe not only the spatiotemporal patterns of neurodevelopment but also the neurobiological mechanisms that underlie them. Human neuroimaging studies have provided evidence for a hierarchical sensorimotor-to-association (S–A) axis of cortical neurodevelopment. Understanding the biological mechanisms that underlie this program of development using traditional neuroimaging approaches has been challenging. Animal models have been used to identify periods of enhanced experience-dependent plasticity – 'critical periods' – that progress along cortical hierarchies and are governed by a conserved set of neurobiological mechanisms that promote and then restrict plasticity. In this review we hypothesize that the S–A axis of cortical development in humans is partly driven by the cascading maturation of critical period plasticity mechanisms. We then describe how recent advances in in vivo neuroimaging approaches provide a promising path toward testing this hypothesis by linking signals derived from non-invasive imaging to critical period mechanisms.
Chemerin triggers migration of a CD8 T cell subset with natural killer cell functions
Authors: Romain Ballet, Melissa LaJevic, Noelle Huskey-Mullin, Rachel Roach, Kevin Brulois, Ying Huang, Muhammad A Saeed, Ha X Dang, Russell K Pachynski, Elizabeth Wilson, Eugene C Butcher, Brian A Zabel
Journal: Molecular Therapy (2023)

The recruitment of cells with effector functions into the tumor microenvironment holds potential for delaying cancer progression. We show that subsets of human CD28-effector CD8 T cells, CCR7
Atractylodinol prevents pulmonary fibrosis through inhibiting TGF-β receptor 1 recycling by stabilizing vimentin
Authors: Mengjiao Hao, Zhuoji Guan, Zhikang Zhang, Haopeng Ai, Xing Peng, Huihao Zhou, Jun Xu, Qiong Gu
Journal: Molecular Therapy (2023)
Biomarkers of aging in frailty and age-associated disorders: State of the art and future perspective
Authors: Stefano Salvioli, Maria Sofia Basile, Leonardo Bencivenga, Sara Carrino, Maria Conte, Sarah Damanti, Rebecca De Lorenzo, Eleonora Fiorenzato, Alessandro Gialluisi, Assunta Ingannato, Angelo Antonini, Nicola Baldini, Miriam Capri, Simone Cenci, Licia Iacoviello, Benedetta Nacmias, Fabiola Olivieri, Giuseppe Rengo, Patrizia Rovere Querini, Fabrizia Lattanzio
Journal: Ageing Research Reviews (2023)

According to the Geroscience concept that organismal aging and age-associated diseases share the same basic molecular mechanisms, the identification of biomarkers of age that can efficiently classify people as biologically older (or younger) than their chronological (i.e. calendar) age is becoming of paramount importance. These people will be in fact at higher (or lower) risk for many different age-associated diseases, including cardiovascular diseases, neurodegeneration, cancer, etc. In turn, patients suffering from these diseases are biologically older than healthy age-matched individuals. Many biomarkers that correlate with age have been described so far. The aim of the present review is to discuss the usefulness of some of these biomarkers (especially soluble, circulating ones) in order to identify frail patients, possibly before the appearance of clinical symptoms, as well as patients at risk for age-associated diseases. An overview of selected biomarkers will be discussed in this regard, in particular we will focus on biomarkers related to metabolic stress response, inflammation, and cell death (in particular in neurodegeneration), all phenomena connected to inflammaging (chronic, low-grade, age-associated inflammation). In the second part of the review, next-generation markers such as extracellular vesicles and their cargos, epigenetic markers and gut microbiota composition, will be discussed. Since recent progresses in omics techniques have allowed an exponential increase in the production of laboratory data also in the field of biomarkers of age, making it difficult to extract biological meaning from the huge mass of available data, Artificial Intelligence (AI) approaches will be discussed as an increasingly important strategy for extracting knowledge from raw data and providing practitioners with actionable information to treat patients.
Incidence of and Factors Associated With Recurrent Firearm Injury Among Patients Presenting to St. Louis Trauma Centers, 2010 to 2019
Authors: Kristen L. Mueller, Benjamin P. Cooper, Vicki Moran, Daphne Lew, Rachel Ancona, Joshua M. Landman, Marguerite Spruce, Phillip Marotta, David B. Liss, Michael A. Mancini, Douglas Schuerer, Megan E. Ranney, Randi E. Foraker
Journal: Annals of Internal Medicine (2023)

Firearm injuries are a public health crisis in the United States.
Circadian biology to advance therapeutics for mood disorders
Authors: Apoorva Bhatnagar, Greg Murray, Sandipan Ray
Journal: Trends in Pharmacological Sciences (2023)

Mood disorders account for a significant global disease burden, and pharmacological innovation is needed as existing medications are suboptimal. A wide range of evidence implicates circadian and sleep dysfunction in the pathogenesis of mood disorders, and there is growing interest in these chronobiological pathways as a focus for treatment innovation. We review contemporary evidence in three promising areas in circadian-clock-based therapeutics in mood disorders: targeting the circadian system informed by mechanistic molecular advances; time-tailoring of medications; and personalizing treatment using circadian parameters. We also consider the limitations and challenges in accelerating the development of new circadian-informed pharmacotherapies for mood disorders.
Mechanotransduction via endothelial adhesion molecule CD31 initiates transmigration and reveals a role for VEGFR2 in diapedesis
Authors: Tao Fu, David P. Sullivan, Annette M. Gonzalez, Maureen E. Haynes, Prarthana J. Dalal, Nakisha S. Rutledge, Abigail L. Tierney, Julia A. Yescas, Evan W. Weber, William A. Muller
Journal: Immunity (2023)
Multiple genes in a single GWAS risk locus synergistically mediate aberrant synaptic development and function in human neurons
Authors: Siwei Zhang, Hanwen Zhang, Marc P. Forrest, Yifan Zhou, Xiaotong Sun, Vikram A. Bagchi, Alena Kozlova, Marc Dos Santos, Nicolas H. Piguel, Leonardo E. Dionisio, Alan R. Sanders, Zhiping P. Pang, Xin He, Peter Penzes, Jubao Duan
Journal: Cell Genomics (2023)

The mechanistic tie between genome-wide association study (GWAS)-implicated risk variants and disease-relevant cellular phenotypes remains largely unknown. Here, using human induced pluripotent stem cell (hiPSC)-derived neurons as a neurodevelopmental model, we identify multiple schizophrenia (SZ) risk variants that display allele-specific open chromatin (ASoC) and are likely to be functional. Editing the strongest ASoC SNP, rs2027349, near
Adding liposomal doxorubicin enhances the abscopal effect induced by radiation/αPD1 therapy depending on tumor cell mitochondrial DNA and cGAS/STING
Authors: Liqun Wang, Ren Luo, Kateryna Onyshchenko, Xi Rao, Meidan Wang, Beatrice Menz, Simone Gaedicke, Anca-Ligia Grosu, Elke Firat, Gabriele Niedermann
Journal: Journal for ImmunoTherapy of Cancer (2023)

Localized radiotherapy (RT) can cause a T cell-mediated abscopal effect on non-irradiated tumor lesions, especially in combination with immune checkpoint blockade. However, this effect is still clinically rare and improvements are highly desirable. We investigated whether triple combination with a low dose of clinically approved liposomal doxorubicin (Doxil) could augment abscopal responses compared with RT/αPD-1 and Doxil/αPD-1. We also investigated whether the enhanced abscopal responses depended on the mitochondrial DNA (mtDNA)/cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING)/IFN-I pathway.We used Doxil in combination with RT and αPD-1 in two tumor models (B16-CD133 melanoma and MC38 colon carcinoma) with mice bearing two tumors, only one of which was irradiated. Mechanistic studies on the role of the mtDNA/cGAS/STING/IFN-I axis were performed using inhibitors and knockout cells in vitro as well as in mice.Addition of a single low dose of Doxil to RT and αPD-1 strongly enhanced the RT/αPD-1-induced abscopal effect in both models. Complete cures of non-irradiated tumors were mainly observed in triple-treated mice. Triple therapy induced more cross-presenting dendritic cells (DCs) and more tumor-specific CD8+ T cells than RT/αPD-1 and Doxil/αPD-1, particularly in non-irradiated tumors. Coincubation of Doxil-treated and/or RT-treated tumor cells with DCs enhanced DC antigen cross-presentation which is crucial for inducing CD8+ T cells. CD8+ T cell depletion or implantation of cGAS-deficient or STING-deficient tumor cells abolished the abscopal effect. Doxorubicin-induced/Doxil-induced IFNβ1 markedly depended on the cGAS/STING pathway. Doxorubicin-treated/Doxil-treated tumor cells depleted of mtDNA secreted less IFNβ1, of the related T cell-recruiting chemokine CXCL10, and ATP; coincubation with mtDNA-depleted tumor cells strongly reduced IFNβ1 secretion by DCs. Implantation of mtDNA-depleted tumor cells, particularly at the non-irradiated/abscopal site, substantially diminished the Doxil-enhanced abscopal effect and tumor infiltration by tumor-specific CD8+ T cells.These data show that single low-dose Doxil can substantially enhance the RT/αPD-1-induced abscopal effect, with a strong increase in cross-presenting DCs and CD8+ tumor-specific T cells particularly in abscopal tumors compared with RT/αPD-1 and Doxil/αPD-1. Moreover, they indicate that the mtDNA/cGAS/STING/IFN-I axis is important for the immunogenic/immunomodulatory doxorubicin effects. Our ﬁndings may be helpful for the planning of clinical radiochemoimmunotherapy trials in (oligo)metastatic patients.
Real-world effectiveness and safety of upadacitinib for the treatment of atopic dermatitis in adult patients switched from dupilumab: A multicenter retrospective study
Authors: Jorge R. Georgakopoulos, Dropen Sheka, Brian Rankin, Khalad Maliyar, Alexander Rimke, Vimal H. Prajapati, Jensen Yeung
Journal: Journal of the American Academy of Dermatology (2023)
The nucleotide-sensing Toll-Like Receptor 9/Toll-Like Receptor 7 system is a potential therapeutic target for IgA nephropathy
Authors: Mingfeng Lee, Hitoshi Suzuki, Kei Ogiwara, Ryosuke Aoki, Rina Kato, Maiko Nakayama, Yusuke Fukao, Yoshihito Nihei, Toshiki Kano, Yuko Makita, Masahiro Muto, Koshi Yamada, Yusuke Suzuki
Journal: Kidney International (2023)

The progression determinants of IgA nephropathy (IgAN) are still not fully elucidated. We have previously demonstrated that the mucosal activation of toll-like receptor (TLR) 9, which senses microbial unmethylated CpG DNA, influences progression by producing aberrantly glycosylated IgA. However, numerous recent reports of patients with IgAN presenting with gross hematuria after the mRNA vaccination for coronavirus disease 2019 suggest that the RNA-sensing system also exacerbates IgAN. Here, we investigated whether TLR7, which recognizes microbial RNA, is also involved in IgAN progression using a murine model and tonsil tissue from 53 patients with IgAN compared to samples from 40 patients with chronic tonsillitis and 12 patients with sleep apnea syndrome as controls. We nasally administered imiquimod, the ligand of TLR7, to IgAN-prone ddY mice and found that TLR7 stimulation elevated the serum levels of aberrantly glycosylated IgA and induced glomerular IgA depositions and proteinuria. Co-administered hydroxychloroquine, which inhibits TLRs, canceled the kidney injuries. In vitro, stimulating splenocytes from ddY mice with imiquimod increased interleukin-6 and aberrantly glycosylated IgA levels. The expression of TLR7 in the tonsils was elevated in patients with IgAN and positively correlated with that of a proliferation-inducing ligand (APRIL) involved in the production of aberrantly glycosylated IgA. Mechanistically, TLR7 stimulation enhanced the synthesis of aberrantly glycosylated IgA through the modulation of enzymes involved in the glycosylation of IgA. Thus, our findings suggest that nucleotide-sensing TLR9 and TLR7 play a crucial role in the pathogenesis of IgAN. Hence, nucleotide-sensing TLRs could be reasonably strong candidates for disease-specific therapeutic targets in IgAN.
Molecular-based targeted therapies in patients with hepatocellular carcinoma and hepato-cholangiocarcinoma refractory to atezolizumab/bevacizumab
Authors: Wendy Limousin, Pierre Laurent-Puig, Marianne Ziol, Nathalie Ganne-Carrié, Pierre Nahon, Amal Ait-Omar, Olivier Seror, Sabrina Sidali, Claudia Campani, Pierre Blanc, Alban Lermine, Laetitia Marisa, Jessica Zucman-Rossi, Jean-Charles Nault
Journal: Journal of Hepatology (2023)
AAV9-mediated SH3TC2 gene replacement therapy targeted to Schwann cells for the treatment of CMT4C
Authors: Elena Georgiou, Alexia Kagiava, Irene Sargiannidou, Natasa Schiza, Marina Stavrou, Jan Richter, Christina Tryfonos, Amanda Heslegrave, Henrik Zetterberg, Christina Christodoulou, Kleopas A Kleopa
Journal: Molecular Therapy (2023)

Type 4C Charcot-Marie-Tooth (CMT4C) demyelinating neuropathy is caused by autosomal recessive SH3TC2 gene mutations. SH3TC2 is highly expressed in myelinating Schwann cells. CMT4C is a childhood-onset progressive disease without effective treatment. Here, we generated a gene therapy for CMT4C mediated by an adeno-associated viral 9 vector (AAV9) to deliver the human SH3TC2 gene in the Sh3tc2
Risk factors for multimorbidity in adulthood: A systematic review
Authors: Clare Tazzeo, Alberto Zucchelli, Davide Liborio Vetrano, Jacopo Demurtas, Lee Smith, Daniel Schoene, Dolores Sanchez-Rodriguez, Graziano Onder, Cafer Balci, Silvia Bonetti, Giulia Grande, Gabriel Torbahn, Nicola Veronese, Alessandra Marengoni
Journal: Ageing Research Reviews (2023)
Toward the Development of User-Centered Neurointegrated Lower Limb Prostheses
Authors: F. Barberi, E. Anselmino, A. Mazzoni, M. Goldfarb, S. Micera
Journal: IEEE Reviews in Biomedical Engineering (2023)

The last few years witnessed radical improvements in lower-limb prostheses. Researchers have presented innovative solutions to overcome the limits of the first generation of prostheses, refining specific aspects which could be implemented in future prostheses designs. Each aspect of lower-limb prostheses has been upgraded, but despite these advances, a number of deficiencies remain and the most capable limb prostheses fall far short of the capabilities of the healthy limb. This paper describes the current state of prosthesis technology; identifies a number of deficiencies across the spectrum of lower limb prosthetic components with respect to users' needs; and discusses research opportunities in design and control that would substantially improve functionality concerning each deficiency. In doing so, the authors present a roadmap of patients related issues that should be addressed in order to fulfill the vision of a next-generation, neurally-integrated, highly-functional lower limb prosthesis.
Long-Term Outcomes of Cardiogenic Shock Complicating Myocardial Infarction
Authors: Lee H. Sterling, Shannon M. Fernando, Robert Talarico, Danial Qureshi, Sean van Diepen, Margaret S. Herridge, Susanna Price, Daniel Brodie, Eddy Fan, Pietro Di Santo, Richard G. Jung, Simon Parlow, Mir B. Basir, Damon C. Scales, Alain Combes, Rebecca Mathew, Holger Thiele, Peter Tanuseputro, Benjamin Hibbert
Journal: Journal of the American College of Cardiology (2023)

Cardiogenic shock secondary to acute myocardial infarction (AMI-CS) is associated with substantial short-term mortality; however, there are limited data on long-term outcomes and trends.This study sought to examine long-term outcomes of AMI-CS patients.This was a population-based, retrospective cohort study in Ontario, Canada of critically ill adult patients with AMI-CS who were admitted to hospitals between April 1, 2009 and March 31, 2019. Outcome data were captured using linked health administrative databases.A total of 9,789 consecutive patients with AMI-CS from 135 centers were included. The mean age was 70.5 ± 12.3 years, and 67.7% were male. The incidence of AMI-CS was 8.2 per 100,000 person-years, and it increased over the study period. Critical care interventions were common, with 5,422 (55.4%) undergoing invasive mechanical ventilation, 1,425 (14.6%) undergoing renal replacement therapy, and 1,484 (15.2%) receiving mechanical circulatory support. A total of 2,961 patients (30.2%) died in the hospital, and 4,004 (40.9%) died by 1 year. Mortality at 5 years was 58.9%. Small improvements in short- and long-term mortality were seen over the study period. Among survivors to discharge, 2,870 (42.0%) required increased support in care from their preadmission baseline, 3,244 (47.5%) were readmitted to the hospital within 1 year, and 1,047 (15.3%) died within 1 year. The mean number of days at home in the year following discharge was 307.9 ± 109.6.Short- and long-term mortality among patients with AMI-CS is high, with minimal improvement over time. AMI-CS survivors experience significant morbidity, with high risks of readmission and death. Future studies should evaluate interventions to minimize postdischarge morbidity and mortality among AMI-CS survivors.
Impact of Sex on Cardiovascular Adaptations to Exercise
Authors: Bradley J. Petek, Eugene H. Chung, Jonathan H. Kim, Rachel Lampert, Benjamin D. Levine, Dermot Phelan, Alfred Danielian, Peter N. Dean, Elizabeth H. Dineen, Antonio B. Fernandez, Mustafa Husaini, Sheela Krishnan, Ankit B. Shah, Katie M. Stewart, Meagan M. Wasfy
Journal: Journal of the American College of Cardiology (2023)